Synlett
DOI: 10.1055/a-2508-9881
letter
Small Molecules in Medicinal Chemistry

An Efficient Synthesis of 3-Aryl-2H-chromene Derivatives as Potential Bone Anabolic Agents

Sonu Khanka
a   Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Kundan S. Rawat
b   Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Priyanka Pandey
b   Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow-226031, India
,
Shyamal Pal
b   Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Ravi P. Vats
b   Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Rajat Rathur
a   Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Kriti Sharma
a   Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Divya Dipali
a   Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Divya Singh
a   Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
,
Atul Goel
b   Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow-226031, India
c   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
› Author Affiliations

This work was supported by the Council of Scientific and Industrial Research, New Delhi, under project MLP-2028. The authors also thank the University Grants Commission (S.K.), the Council of Scientific and Industrial Research (K.S.R. and S.P.), the Department of Science and Technology (P.P. and K.S.), and the Department of Biotechnology (R.R.) for research fellowships.


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Abstract

In a quest to identify new osteogenic agents, a new series of 3-aryl-2H-chromene derivatives were rationally designed based on natural isoflavonoids and synthesized through ring transformation of 2H-pyran-2-ones with 3-acetyl-2H-chromene derivatives. From primary screening, five compounds were found to be active in osteoblast differentiation. Among these, the most active compound, 3-(7-methoxy-2H-chromen-3-yl)-5-piperidin-1-ylbiphenyl-4-carbonitrile, showed significantly enhanced calcium nodule formation at 1 pM and 100 pM, and increased osteoblast cell viability. Western blotting experiments indicate that this chromene upregulated osteogenic marker genes such as RUNX2, BMP2, and Type 1 col at the transcriptional and translational levels at concentrations of 1 pM and 100 pM. Furthermore, it decreased osteoblast cell apoptosis at 1 pM and 100 pM, while increasing cell survival in serum-deprived conditions. All these results suggested that the compound has great potential as a bone anabolic agent to improve bone health.

Supporting Information



Publication History

Received: 09 November 2024

Accepted: 30 December 2024

Accepted Manuscript online:
30 December 2024

Article published online:
10 February 2025

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